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      • KCI등재

        캡사이신유도체를 함유하는 폴록사머 겔제제의 물리화학적 특성 : based Gel Containing Capsaicin Analog

        김태완,조청일,최춘영,이범진 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

        Physicochemical changes of poloxamer-based gel containing capsaicin analog (N-[3-(3,4-dimethylphenyl)propyl]-4-(2-aminoethoxy)-3-methoxypheny] acetamide) such as drug content, viscosity and surface tension were investigated during the storage conditions at three different temperatures (25, 40 and 60℃) over 90 days. No noticeable changes of color were observed when stored at 25 and 40℃. However, the color of white poloxamer gels turned yellow during storage at 60℃. The drug contents were unchanged during storage at 25℃ but had tendency to decrease at 40℃. The drug contents were highly decreased over 40-50% when stored at 60℃. The viscosity of a poloxamer-based gel was unchanged during storage at 25 and 40℃ but greatly increased at 60℃. The surface tension of a poloxamer-based gel was not changed at three different temperatures. The storage conditions of a poloxamer-based gel containing capsaicin analog can be considered for further clinical applications.

      • SCIESCOPUSKCI등재

        Effect of Solvents on Physical Properties and Release Characteristics of Monolithic Hydroxypropylmethylcellulose Matrix Granules and Tablets

        Cao Qing-Ri,Choi Yun-Woong,Cui Jing-Hao,Lee Beom-Jin The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.4

        Effect of solvents on physical characteristics and release characteristics of monolithic acetaminophen (APAP) hydroxypropylmethylcellulose (HPMC) matrix granules and tablets were examined. Various types and amounts of solvents were employed for granulation and coating. APAP and other excipients were mixed and were then wet-granulated in a high-speed mixer. The dried granules were then directly compressed and film-coated with low viscosity grade HPMC. As the amount of water increased, the size of granules also increased, showing more spherical and regular shape. However, manufacturing problems such as capping and lamination in tableting occurred when water was used alone as a granulating solvent. The physical properties of HPMC matrix granules were not affected by the batch size. The initial release rate as well as the amount of APAP dissolved had a tendency to decrease as the water level increased. Addition of nonaqueous solvent like ethanol to water resulted in good physical properties of granules. When compared to water/ethanol as a coating solvent, the release rate of film-coated HPMC matrix tablets was more sensitive to the conditions of coating and drying in methylene chloride/ethanol. Most of all, monolithic HPMC matrix tablet when granulated in ethanol/water showed dual release with about $50\%$ drug release immediately within few minutes followed by extended release. It was evident that the type and amount of solvents (mainly water and ethanol) were very important for wet granulation and film-coating of monolithic HPMC matrix tablet, because the plastic deforming and fragmenting properties of material were changed by the different strengths of the different solvents.

      • Circadian variations in the pharmacokinetics, tissue distribution and urinary excretion of nifedipine after a single oral administration to rats

        Cao, Qing-Ri,Kim, Tae-Wan,Choi, Jun Shik,Lee, Beom-Jin John Wiley Sons, Ltd. 2005 Biopharmaceutics & drug disposition Vol.26 No.9

        <P>Circadian variations in the pharmacokinetics, tissue distribution and urinary excretion of nifedipine were examined in fasted rats after administering a single oral dose at three different dosing times (08:00 am, 16:00 pm, 00:00 am). The plasma concentrations, the areas under the plasma concentration-time curve from zero to 6 h (AUC<SUB>0–6 h</SUB>) and the peak plasma concentration (C<SUB>max</SUB>) were significantly higher in the rats dosed at 08:00 am (immediately inactive), and was lower at 16:00 pm (most inactive) and 00:00 am (most active). The time to reach the C<SUB>max</SUB> (T<SUB>max</SUB>) was the shortest in the rats dosed at 08:00 am. It was very interesting to observe the double peak phenomena in the plasma concentration profiles, showing a larger peak followed by a smaller peak. There was a dosing time dependency on the tissue distribution 30 min after administration, showing a similar tendency to the pharmacokinetic behavior. However, there was no distinct dosing time dependency observed at 2 h after administration due to the extensive disposition. The cumulative urine excretion of nifedipine in the rats dosed at 08:00 am was significantly higher (about two-fold) than in those dosed at 16:00 pm and 00:00 am. The pharmacokinetics of nifedipine in the rats was consistent with that observed in human subjects in terms of the day–night clock time but the biological time was the opposite, as marked by the rest–activity cycles. These results may help to explain the circadian time-dependency of nifedipine pharmacokinetics. Copyright © 2005 John Wiley & Sons, Ltd.</P>

      • KCI등재

        Effect of Solvents on Physical Properties and Release Characteristics of Monolithic Hydroxypropylmethylcellulose Matrix Granules and Tablets

        Qing-Ri Cao,최연웅,Jing-Hao Cui,Beom-Jin Lee 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.4

        Effect of solvents on physical characteristics and release characteristics of monolithic acetaminophen (APAP) hydroxypropylmethylcellulose (HPMC) matrix granules and tablets were examined. Various types and amounts of solvents were employed for granulation and coating. APAP and other excipients were mixed and were then wet-granulated in a high-speed mixer. The dried granules were then directly compressed and film-coated with low viscosity grade HPMC. As the amount of water increased, the size of granules also increased, showing more spherical and regular shape. However, manufacturing problems such as capping and lamination in tableting occurred when water was used alone as a granulating solvent. The physical properties of HPMC matrix granules were not affected by the batch size. The initial release rate as well as the amount of APAP dissolved had a tendency to decrease as the water level increased. Addition of nonaqueous solvent like ethanol to water resulted in good physical properties of granules. When compared to water/ethanol as a coating solvent, the release rate of film-coated HPMC matrix tablets was more sensitive to the conditions of coating and drying in methylene chloride/ethanol. Most of all, monolithic HPMC matrix tablet when granulated in ethanol/ water showed dual release with about 50% drug release immediately within few minutes followed by extended release. It was evident that the type and amount of solvents (mainly water and ethanol) were very important for wet granulation and film-coating of monolithic HPMC matrix tablet, because the plastic deforming and fragmenting properties of material were changed by the different strengths of the different solvents.

      • KCI등재

        가용화 조성물을 함유한 PVP형 고체분산체의 제조 및 특성 : Based Solid Dispersion Systems Containing Solubilizers

        Cao, Qing-Ri,김태완,최춘영,권경애,이범진 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

        The PVP-based solid dispersion systems (SDs) containing lovastatin (LOS) and solubilizers (sodium lauryl sulfate, tween 80 and oleic acid) were prepared to enhance dissolution rate of practically water insoluble LOS using solvent evaporation method. Two different organic cosolvents either acetone/ethanol or acetonitrile/ethanol were used for the preparation of SDs. The LOS contents were highly decreased when acetone/ethanol cosolvents were used. The decrease of LOS contents was not caused by acetonitrile or acetone, based on HPLC data. The surface morphology as investigated by scanning electron microscope (SEM) and angle of repose as an index of flowability of SDs were highly dependent of the type and amount of solubilizers used. Base on differential scanning calorimetry (DSC) and X-ray powder diffraction data, the SDs made crystalline LOS into amorphous structure or partially eutectic mixtures. The simultaneous use of the solubilizers in SDs was also useful to increase dissolution rate of LOS in gastric or intestinal fluid. The SDs containing solubilizers reached 76% and 60% in gastric and intestinal fluid, respectively but the commercial tablet gave only less that 4%. These solubilizers in SDs could be also applicable for enhancing dissolution and bioavailability of poorly water-soluble drugs.

      • KCI등재

        Physicochemical characterization and cytotoxicity of chitosanmodified single walled carbon nanotubes as drug carriers

        Qing‑Ri Cao,Xiao‑Xue Zhang,Hao‑Yan Huang,Li‑Qing Chen,Hehua Jin,Beom‑Jin Lee,Jing‑Hao Cui 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.1

        The application of single-walled carbon nanotubes (SWCNTs) as drug carriers is limited by their poor dispersal in aqueous medium. This study aimed to prepare chitosan (CS)-modified SWCNTs (CS-SWCNTs) and to evaluate their physicochemical properties and cytotoxicity. Oxidized SWCNTs (O-SWCNTs) were prepared with the use of strong acid, and the effects of acidizing conditions on the oxidation degree of the O-SWCNTs were investigated. CS was then non-covalently modified on the surfaces of O-SWCNTs. O-SWCNTs and CS-SWCNTs were characterized through ultraviolet spectroscopy, Fourier transform-infrared spectroscopy, Raman spectroscopy, and transmission electron microscopy. The cytotoxic effects of the functionalized SWCNTs were determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. O-SWCNTs with relatively complete structure were successfully synthesized through 5 h of treatment with 5 M acid. The amine group of the CS and the carboxyl group of O-SWCNTs interacted in CS-SWCNTs. The functionalized SWCNTs did not aggregate or precipitate in water and exerted no cytotoxic effects on A549 and MCF-7 tumor cells. The CS-SWCNTs possess the advantages of a simple preparation process, excellent water dispersibility, and biocompatibility for drug loading.

      • KCI등재

        Determination of Highly Soluble L-Carnitine in Biological Samples by Reverse Phase High Performance Liquid Chromatography with Fluorescent Derivatization

        Qing-Ri Cao,Shan Ren,Mi-Jin Park,Yun-Jaie Choi,Beom-Jin Lee 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8

        This study was performed in order to validate an effective high performance liquid chromatograpy (HPLC) method to determine L-carnitine in biological samples such as plasma, milk and muscle in cows. An L-carnitine derivative for fluorescence absorption was synthesized with 1-aminoanthracene (16 mg/mL in acetone) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC; 160 mg/mL in 0.01 M NaH2PO4 buffer) as a precolumn fluorescent derivative reagent. γ-Butyrobetaine HCl was used as an internal standard. A reversedphase column with fluorescence detection at the excitation and emission wavelengths of 248 and 418 nm were used. The mobile phase consisted of 30% acetonitrile with 0.1 M ammonium acetate in water (pH 3.5) adjusted with acetic acid and delivered at a flow rate of 1.5 mL/ min. The L-carnitine concentration in plasma, milk and muscle samples of cows after oral feeding with 24 g L-carnitine/day for 2 months was then determined. All biological samples were deproteinated by barium hydroxide and zinc sulfate heptahydrate before the derivative reaction. Blank cow plasma was dialyzed using cellulose membrane for standard calibration. The calibration curve showed good linearity (r2 >0.999) over the concentration range of 50 to 5000 ng/mL. The precision and accuracy were also satisfactory with less than 15% intra- and interday coefficiency of variations. The peaks of L-carnitine and internal standard in HPLC chromatography were successfully separated in plasma, milk and muscle samples of cows. The current derivatization method of L-carnitine for fluorescence detection was simple and adequately sensitive and could be applied to determine L-carnitine in biological samples.

      • SCIESCOPUSKCI등재

        Determination of Highly Soluble L-Carnitine in Biological Samples by Reverse Phase High Performance Liquid Chromatography with Fluorescent Derivatization

        Cao, Qing-Ri,Ren, Shan,Park, Mi-Jin,Choi, Yun-Jaie,Lee, Beom-Jin 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8

        This study was performed in order to validate an effective high performance liquid chromatograpy (HPLC) method to determine L-carnitine in biological samples such as plasma, milk and muscle in cows. An L-carnitine derivative for fluorescence absorption was synthesized with 1-aminoanthracene (16 mg/mL in acetone) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC: 160 mg/mL in 0.01 M $NaH_2PO_4$ buffer) as a precolumn fluorescent derivative reagent. ${\gamma}-Butyrobetaine$ HCI was used as an internal standard. A reversed-phase column with fluorescence detection at the excitation and emission wavelengths of 248 and 418 nm were used. The mobile phase consisted of 30% acetonitrile with 0.1 M ammonium acetate in water (pH 3.5) adjusted with acetic acid and delivered at a flow rate of 1.5 mL/min. The L-carnitine concentration in plasma, milk and muscle samples of cows after oral feeding with 24 g L-carnitine/day for 2 months was then determined. All biological samples were deproteinated by barium hydroxide and zinc sulfate heptahydrate before the derivative reaction. Blank cow plasma was dialyzed using cellulose membrane for standard calibration. The calibration curve showed good linearity ($r^2$ >0.999) over the concentration range of 50 to 5000 ng/mL. The precision and accuracy were also satisfactory with less than 15% intra- and inter- day coefficiency of variations. The peaks of L-carnitine and internal standard in HPLC chromatography were successfully separated in plasma, milk and muscle samples of cows. The current derivatization method of L-carnitine for fluorescence detection was simple and adequately sensitive and could be applied to determine L-carnitine in biological samples.

      • KCI등재

        Scratching Stimuli of Mycelia Influence Fruiting Body Production and ROS-Scavenging Gene Expression of Cordyceps militaris

        ( Gui-qing Liu ),( Xue-hong Qiu ),( Li Cao ),( Ri-chou Han ) 한국균학회 2018 Mycobiology Vol.46 No.4

        The entomopathogenic fungus Cordyceps militaris is a valuable medicinal ascomycete, which degenerates frequently during subsequent culture. To avoid economic losses during industrialized production, scratching stimuli of mycelia was introduced to improve the fruiting body production. The present results indicated that higher yields and biological efficiency were obtained from two degenerate strains (YN1-14 and YN2-7) but not from g38 (an insertional mutant in Rhf1 gene with higher yields and shorter growth periods). Furthermore, the growth periods of the fruiting bodies were at least 5 days earlier when the mycelia were scratched before stromata differentiation. Three ROS-scavenging genes including Cu/Zn superoxide dismutase (CmSod1), Glutathione peroxidase (CmGpx), and Catalase A (CmCat A) were isolated and their expression profiles against scratching were determined in degenerate strain YN1-14 and mutant strain g38. At day 5 after scratching, the expression level of CmGpx significantly decreased for strain g38, but that of CmSod1 significantly increased for YN1-14. These results indicated that scratching is an effective way to promote fruiting body production of degenerate strain, which may be related at least with Rhf1 and active oxygen scavenging genes.

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